表觀遺傳調控 (Epigenetic modification)可經由修飾組蛋白上的胺基酸來影響基因轉錄的活性，常見的修飾包含了DNA甲基化(DNA methylation)、組蛋白修飾(Histone modification)以及染色質的重塑(Chromatin remodeling)。最近的研究數據顯示表觀遺傳調控會藉由影響染色質的重塑來調控基因轉錄的活性，這些調控和記憶、學習以及認知有關。組蛋白去乙醯化調控因子Histone deacetylase (HDAC)的抑制劑已經被證實可以用來改善神經退化疾病的老鼠的表現型，像是亨丁頓舞蹈症及阿茲海默症。
為了瞭解發育過程中組蛋白甲基化在神經生成所扮演的角色，我們提出一個方法系統性地去研究EHMT2在神經發育分化過程中的影響。 EHMT2(G9a) 是一種常染色質的甲基轉移酶，它能藉由甲基化組蛋白H3K9來調控轉錄的活性。在in vitro實驗中，我們以G9a的抑制劑BIX-01294處理老鼠的神經幹細胞 (mNSC)，發現在同時加有HDAC抑制劑Valproic acid和BIX-01294的細胞中，Tuj1、Nfm和NeuroD1表現量明顯的比單獨加Valproic acid或BIX-01294增加許多，顯示組蛋白甲基化和乙醯化之間具有協同作用可以幫助神經幹細胞的分化。而在in vivo的實驗中，我們將HDAC抑制劑SAHA與BIX-01294經由腹腔注到三個月大的成年小鼠中，發現在小鼠大腦的Subventricular zone中的 doublecortin表現有明顯的增加。這結果顯示BIX-01294和SAHA可以促進小鼠腦中的Subventricular zone的神經幹細胞分化成新的神經元。

Chromatin and epigenetic modifications play a central role in maintaining the gene expression programs that are important for both self-renewal and cell commitment. Recent research indicates that epigenetic modification may be integral to the cell fate commitment of neural stem cells. However, the molecules that are involved in this mechanism are not fully elucidated. Here we isolate mouse neuron stem cell (mNSC) from mouse embryonic brain (E11.5) and exposed mouse NSCs in vitro to HDAC inhibitors, valproic acid and sodium butyrate and a histone methyltransferase EHMT2 (G9a) inhibitor, BIX-01294, respectively, and analyzed their effects on mNSC differentiation. Both HDAC inhibitors and BIX-01294 enhance neuronal differentiation of mNSC which were characterized by increased elongation of neurites and increased expression of neuronal genes including Tuj1, Nfm and neuroD1. Expression of the synaptic proteins Synapsin and Synaptophysin which regulate release of neurotransmitter was increased in mNSC treated with valproic acid and is further increased in mNSC co-treated with valproic and BIX-01294. By delivering a HDAC inhibitor Suberoylanilide hydroxamic acid (SAHA) or BIX-01294 intraperitoneally in to adult mice, we show that expression of the young neuron marker doublecortin is significantly increased in the subventricular zone of lateral ventricle. Our results suggest that chromatin is dynamically remodeled during neurogenesis, and that di-methylation of histone H3 by Ehmt2 is associated with NSC self-renew in vitro and in vivo.

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